What is so super about ageing?
Authors: Alexandra Touroutoglou, Bonnie Wong, Joseph M Andreano
Journal: The Lancet Healthy Longevity (2023)

Research data on ageing show that age-related cognitive decline is not inevitable. Studies have identified a remarkable group of older adults who display a youthful memory function—superagers.1Sun FW Stepanovic MR Andreano J Barrett LF Touroutoglou A Dickerson BC Youthful brains in older adults: preserved neuroanatomy in the default mode and salience networks contributes to youthful memory in superaging.J Neurosci. 2016; 36: 9659-9668Crossref PubMed Scopus (104) Google Scholar, 2Zhang J Andreano JM Dickerson BC Touroutoglou A Barrett LF Stronger functional connectivity in the default mode and salience networks is associated with youthful memory in superaging.Cereb Cortex. 2020; 30: 72-84Crossref PubMed Scopus (27) Google Scholar, 3Katsumi Y Wong B Cavallari M et al.Structural integrity of the anterior mid-cingulate cortex contributes to resilience to delirium in SuperAging.Brain Commun. 2022; 4fcac163Crossref Scopus (1) Google Scholar, 4Harrison TM Weintraub S Mesulam MM Rogalski E Superior memory and higher cortical volumes in unusually successful cognitive aging.J Int Neuropsychol Soc. 2012; 18: 1081-1085Crossref PubMed Scopus (52) Google Scholar, 5Harrison TM Maass A Baker SL Jagust WJ Brain morphology, cognition, and β-amyloid in older adults with superior memory performance.Neurobiol Aging. 2018; 67: 162-170Crossref PubMed Scopus (8) Google Scholar, 6Dang C Yassi N Harrington KD et al.Rates of age- and amyloid beta-associated cortical atrophy in older adults with superior memory performance.Alzheimers Dement (Amst). 2019; 11: 566-575Crossref PubMed Scopus (16) Google Scholar In The Lancet Healthy Longevity, Marta Garo-Pascual and colleagues7Garo-Pascual M Gaser C Zhang L Tohka J Medina M Strange BA Brain structure and phenotypic profile of superagers compared with age-matched older adults: an analysis from the Vallecas Project.Lancet Healthy Longev. 2023; (published online July 13.)https://doi.org/10.1016/S2666-7568(23)00079-XGoogle Scholar add to this line of research by using the rich data from the Vallecas Project, an ongoing longitudinal cohort study based in Madrid, Spain, to explore the neuroanatomy, characteristics, and resilience to Alzheimer's disease in adults classified as superagers. The study advances superageing research, providing a better understanding of the phenotype of this subpopulation of older adults. This phenotype includes several previously unobserved differences between superagers and typical older adults across multiple domains, including motor skills and mental health. The examination of superagers in a Spanish-speaking cohort also expands the literature on this topic by potentially increasing the generalisability of results beyond native English speakers. However, it should be noted that the inclusion criteria used to define superagers in Garo-Pascual and colleagues' study differs from those used in foundational research, which hinders comparisons between these results and those of other studies. Traditionally, superagers have been defined using delayed recall performance on verbal list learning tasks, such as the Rey Auditory Verbal Learning Task,4Harrison TM Weintraub S Mesulam MM Rogalski E Superior memory and higher cortical volumes in unusually successful cognitive aging.J Int Neuropsychol Soc. 2012; 18: 1081-1085Crossref PubMed Scopus (52) Google Scholar the California Verbal Learning Task,1Sun FW Stepanovic MR Andreano J Barrett LF Touroutoglou A Dickerson BC Youthful brains in older adults: preserved neuroanatomy in the default mode and salience networks contributes to youthful memory in superaging.J Neurosci. 2016; 36: 9659-9668Crossref PubMed Scopus (104) Google Scholar, 2Zhang J Andreano JM Dickerson BC Touroutoglou A Barrett LF Stronger functional connectivity in the default mode and salience networks is associated with youthful memory in superaging.Cereb Cortex. 2020; 30: 72-84Crossref PubMed Scopus (27) Google Scholar, 5Harrison TM Maass A Baker SL Jagust WJ Brain morphology, cognition, and β-amyloid in older adults with superior memory performance.Neurobiol Aging. 2018; 67: 162-170Crossref PubMed Scopus (8) Google Scholar, 6Dang C Yassi N Harrington KD et al.Rates of age- and amyloid beta-associated cortical atrophy in older adults with superior memory performance.Alzheimers Dement (Amst). 2019; 11: 566-575Crossref PubMed Scopus (16) Google Scholar or the Hopkins Verbal Learning Task,3Katsumi Y Wong B Cavallari M et al.Structural integrity of the anterior mid-cingulate cortex contributes to resilience to delirium in SuperAging.Brain Commun. 2022; 4fcac163Crossref Scopus (1) Google Scholar on which superagers aged between 65–80 years or older perform equivalently to middle-aged adults (50–60 years old)4Harrison TM Weintraub S Mesulam MM Rogalski E Superior memory and higher cortical volumes in unusually successful cognitive aging.J Int Neuropsychol Soc. 2012; 18: 1081-1085Crossref PubMed Scopus (52) Google Scholar, adults aged 30–44 years,6Dang C Yassi N Harrington KD et al.Rates of age- and amyloid beta-associated cortical atrophy in older adults with superior memory performance.Alzheimers Dement (Amst). 2019; 11: 566-575Crossref PubMed Scopus (16) Google Scholar or young adults (18–32 years old).1Sun FW Stepanovic MR Andreano J Barrett LF Touroutoglou A Dickerson BC Youthful brains in older adults: preserved neuroanatomy in the default mode and salience networks contributes to youthful memory in superaging.J Neurosci. 2016; 36: 9659-9668Crossref PubMed Scopus (104) Google Scholar, 2Zhang J Andreano JM Dickerson BC Touroutoglou A Barrett LF Stronger functional connectivity in the default mode and salience networks is associated with youthful memory in superaging.Cereb Cortex. 2020; 30: 72-84Crossref PubMed Scopus (27) Google Scholar, 3Katsumi Y Wong B Cavallari M et al.Structural integrity of the anterior mid-cingulate cortex contributes to resilience to delirium in SuperAging.Brain Commun. 2022; 4fcac163Crossref Scopus (1) Google Scholar, 5Harrison TM Maass A Baker SL Jagust WJ Brain morphology, cognition, and β-amyloid in older adults with superior memory performance.Neurobiol Aging. 2018; 67: 162-170Crossref PubMed Scopus (8) Google Scholar By contrast, Garo-Pascual and colleagues defined their cohort using the Free and Cued Selective Reminding Test, which involves learning and retrieval mechanisms that differ significantly from list-learning tests (ie, this test involves elaborative processing during learning which may lead to better recall performance). Although the California Verbal Learning Task, the Rey Auditory Verbal Learning Task, and the Hopkins Verbal Learning Task are similar in their learning and retrieval processes and highly correlated,8Crossen JR Wiens AN Comparison of the Auditory-Verbal Learning Test (AVLT) and California Verbal Learning Test (CVLT) in a sample of normal subjects.J Clin Exp Neuropsychol. 1994; 16: 190-194Crossref PubMed Google Scholar, 9Lacritz LH Cullum CM The Hopkins Verbal Learning Test and CVLT: a preliminary comparison.Arch Clin Neuropsychol. 1998; 13: 623-628PubMed Google Scholar strong associations between the Free and Cued Selective Reminding Test and these list-learning measures have not been reported. Thus, superagers defined by differing measures might not be directly comparable and could explain divergent neuroimaging results in the present study. Garo-Pascual and colleagues used an age range different from that used in previous superaging studies, and used the Digit Symbol Substitution Test instead of Trail Making Test part B for non-memory assessment. The findings of this study also differ from those of previous research in one noteworthy respect. The authors report less grey matter loss in multiple brain regions typically associated with learning and memory, primarily in the medial temporal lobe, which is consistent with previous research. However, the authors did not report data on the neuroanatomical preservation of a structure that has been repeatedly observed in superagers since the foundational studies on the topic: the anterior mid-cingulate cortex. Previous studies have reported greater cortical thickness and better brain network functional connectivity in the anterior mid-cingulate cortex in superagers than in age-matched peers.1Sun FW Stepanovic MR Andreano J Barrett LF Touroutoglou A Dickerson BC Youthful brains in older adults: preserved neuroanatomy in the default mode and salience networks contributes to youthful memory in superaging.J Neurosci. 2016; 36: 9659-9668Crossref PubMed Scopus (104) Google Scholar, 2Zhang J Andreano JM Dickerson BC Touroutoglou A Barrett LF Stronger functional connectivity in the default mode and salience networks is associated with youthful memory in superaging.Cereb Cortex. 2020; 30: 72-84Crossref PubMed Scopus (27) Google Scholar, 3Katsumi Y Wong B Cavallari M et al.Structural integrity of the anterior mid-cingulate cortex contributes to resilience to delirium in SuperAging.Brain Commun. 2022; 4fcac163Crossref Scopus (1) Google Scholar, 4Harrison TM Weintraub S Mesulam MM Rogalski E Superior memory and higher cortical volumes in unusually successful cognitive aging.J Int Neuropsychol Soc. 2012; 18: 1081-1085Crossref PubMed Scopus (52) Google Scholar, 5Harrison TM Maass A Baker SL Jagust WJ Brain morphology, cognition, and β-amyloid in older adults with superior memory performance.Neurobiol Aging. 2018; 67: 162-170Crossref PubMed Scopus (8) Google Scholar Additionally, our own group has also demonstrated that both the thickness and degree of connectivity of the anterior mid-cingulate cortex—"an important region involved in the neurocircuitry of underlying successful ageing"5Harrison TM Maass A Baker SL Jagust WJ Brain morphology, cognition, and β-amyloid in older adults with superior memory performance.Neurobiol Aging. 2018; 67: 162-170Crossref PubMed Scopus (8) Google Scholar—predict better memory performance in both superagers and typical older adults.1Sun FW Stepanovic MR Andreano J Barrett LF Touroutoglou A Dickerson BC Youthful brains in older adults: preserved neuroanatomy in the default mode and salience networks contributes to youthful memory in superaging.J Neurosci. 2016; 36: 9659-9668Crossref PubMed Scopus (104) Google Scholar, 2Zhang J Andreano JM Dickerson BC Touroutoglou A Barrett LF Stronger functional connectivity in the default mode and salience networks is associated with youthful memory in superaging.Cereb Cortex. 2020; 30: 72-84Crossref PubMed Scopus (27) Google Scholar The anterior mid-cingulate cortex is a densely connected hub sitting at the intersection of brain networks that are preserved in superageing1Sun FW Stepanovic MR Andreano J Barrett LF Touroutoglou A Dickerson BC Youthful brains in older adults: preserved neuroanatomy in the default mode and salience networks contributes to youthful memory in superaging.J Neurosci. 2016; 36: 9659-9668Crossref PubMed Scopus (104) Google Scholar, 2Zhang J Andreano JM Dickerson BC Touroutoglou A Barrett LF Stronger functional connectivity in the default mode and salience networks is associated with youthful memory in superaging.Cereb Cortex. 2020; 30: 72-84Crossref PubMed Scopus (27) Google Scholar, 5Harrison TM Maass A Baker SL Jagust WJ Brain morphology, cognition, and β-amyloid in older adults with superior memory performance.Neurobiol Aging. 2018; 67: 162-170Crossref PubMed Scopus (8) Google Scholar and involved in a variety of functions including attention, memory, executive function, and motivation.10Touroutoglou A Andreano J Dickerson BC Barrett LF The tenacious brain: how the anterior mid-cingulate contributes to achieving goals.Cortex. 2020; 123: 12-29Crossref PubMed Scopus (10) Google Scholar Thus, the greater performance of superagers relative to typical older adults might not only be a result of better memory function but could also reflect differences in motivation, executive function, and persistence in the face of difficulty,10Touroutoglou A Andreano J Dickerson BC Barrett LF The tenacious brain: how the anterior mid-cingulate contributes to achieving goals.Cortex. 2020; 123: 12-29Crossref PubMed Scopus (10) Google Scholar which suggests that superagers have a higher level of tenacity than typical older adults. Future studies should measure motivation and persistence in superagers to explore this possibility. The findings of Garo-Pascual and colleagues study are consistent with reports of resilience to Alzheimer's disease in superageing, although the mechanisms underlying this resilience remain unknown. More efforts are needed to refine and harmonise definitions of superageing in multisite studies using large and diverse cohorts. Large-scale studies will allow further exploration of resilience factors in superagers, which could lead to new insights in the prevention of age-related memory decline. Research reported in this publication was supported by the National Institutes of Health (NIH) under award numbers K23 DC016912, R21AG080588, R01AG071173 and R21AG061743. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Brain structure and phenotypic profile of superagers compared with age-matched older adults: a longitudinal analysis from the Vallecas ProjectFactors associated with dementia prevention are also relevant for resistance to age-related memory decline and brain atrophy, and the association between superageing and movement speed could provide potential novel insights into how to preserve memory function into the ninth decade. Full-Text PDF Open Access